Kidney dialysis covers both extra-corporeal (hemodialysis etc.) and intra-corporeal (peritoneal dialysis) modalities. Peritoneal dialysis is a well-established medical procedure for correcting end stage renal failure (ESRF). The principles of operation of peritoneal dialysis start with initial drain, followed by fill, dwell and drain, known as a cycle. Classification of peritoneal dialysis therapy are based on the number of cycles (fill, dwell and drain), the fill volume of dialysis fluid used per cycle, the time of treatment and whether the operation is done manually or with a machine.
Machine or automatic operations are done mostly at night using cyclers, also known as automated peritoneal dialysis (APD) machines. APD machines normally utilize 3, 5 or 15-liter pre-sterilized fluid containers (bags).
The majority of peritoneal dialysis patients are using manual peritoneal dialysis therapy, termed continuous ambulatory peritoneal dialysis (CAPD). CAPD is performed during the day and utilizes pre-sterilized 2 liters or less, fluid bags. Application of CAPD requires instillation of about two liters of prepackaged fresh sterile dialysate into the peritoneal cavity every 4 to 6 hours during 24 hours of treatment, 7 days per week.
Associated disposable peritoneal dialysis sets and the operational techniques for APD and CAPD modalities are significantly different. The sets for CAPD are very simple for manual manipulations. However, sets for APD machines are functionally complex in design and operation.
Due to the increased utilization of peritoneal dialysis for treating patients with ESRF, there is a need to provide better products to advance this medical treatment. Because of the low annual operating cost of peritoneal dialysis, coupled with initial clinical benefits, peritoneal dialysis is becoming the first choice of dialysis therapy in the developing world.
There is an urgent need to provide biocompatible peritoneal dialysis fluids and efficient techniques that could prolong the viability of the peritoneal membrane. The current art formulates media as a completed product in a single storage container. The conventional peritoneal dialysis solutions are known to be bio-incompatible because of low pH (acidic), lactate, glucose degradation products (high concentrations), and osmolality (glucose based). In addition, poor connectors, poor tubing sets and open operational systems result in frequent and/or higher peritonitis (infection) rates.
During the past decade, products have been introduced to reduce peritoneal infection rates from one episode in nine months to the current lower rate of one episode in two years or more. For example, see International Publication Nos. WO80/02706, WO 2006/001962 and WO 2010/096657; U.S. Pat. Nos. 4,326,526, 4,902,282, 7,736,328, 7,208,479, 7,243,893, 7,311,886, 7,122,210, 7,169,303, 7,175,606, 7,198,611, 6,919,326, 6,986,872, 7,011,855, 7,053,059 and 5,053,003; and U.S. Patent Application Publication Nos. 2005/0020507, 2006/0172954, 2008/0125693 and 2010/0069817,
One of the main focuses has been on the peritoneal dialysis set itself. The major contributing products are the disinfectant caps for capping the tubing, the “Y” Set™ and the double bag system, to name a few. The “Y” Set™ includes an empty bag and connected tubes shaped like a “Y” dictating the flow of dialysis solution. Additionally, a bag filled with peritoneal dialysis solution is connected to this system. First of all, the used dialysis solution is drained into the empty bag, carrying possible bacteria from the catheter connector. Then fresh dialysis solution is flushed through the tubes and into the bag for about three seconds. The connection to the abdominal cavity remains closed during this procedure. When the tubes have been flushed, the patient's catheter connector is opened and fresh peritoneal dialysis solution is introduced into the cavity (flush-before-fill principle). Depending on the system, the flow of peritoneal dialysis solution (drainage, flush, filling) is controlled with clamps or a disc. The current double bag system uses a single container filled with dialysate and a second empty container (often of an inferior quality) used as a drain container. These products have helped to extend the effective lifetime of the peritoneal membrane and thus have prolonged peritoneal dialysis modality for the average patient. These products have also reduced the medical complications, hospitalizations and the annual treatment cost per patient. However, the search to perfect peritoneal dialysis treatment still continues. A significant number of the new dialysate packages have been targeted to CAPD patients but because CAPD is a manual operation, some of the regulatory bodies have not accepted the operational safety of the proposed new packages. Improvements to the current art teach formulation separations and/or specific partitions of dialysate. They all use different compartments in a single bag to house the separated parts that are later admixed to produce the final dialysate. For example, U.S. Pat. No. 7,243,893 relates to a compartmentalized single bag. Manufacturing processes are complex and hence the final products cost almost twice as much as the standard dialysate bags. Significantly, none of the prior art teaches any novel methods for administering additives.
Another main focus that has been, and is still undergoing extensive studies, is dialysate. It is also one of the highest costs, but essential parts, of the therapy. Dialysate may be considered as media made of multiple compositions. Commercial dialysate are formulated into a single bag, manufactured in individual container sizes, distributed and stocked until usage. However, the compounds in these commercially finished prepackaged compositions are not chemically and physically stable. It is well known in the art that some of the compounds in dialysate are catalysts that may speed up the breakdown of their companion compounds. Under certain conditions, some compounds may also induce undesirable precipitations of some of the other compounds in the dialysate. Examples of unstable compounds are glucose which undergoes caramelization and/or breakdown and bicarbonate, which precipitates. Undesirable by-products produced by caramelization of glucose (as stated previously above) during sterilization and storage; produce harmful effects on the peritoneal membrane.
In order to stabilize glucose in dialysate, hydrochloric acid, acetic acid and lactic acid are added to the solution to lower the pH of the composite dialysate (calcium, sodium, potassium, chloride etc.), to a pH of 5.3. It is known that current acidic dialysate causes infusion pain and gradually destroys the peritoneal membrane. And, even at this acidic level, glucose still undergoes caramelization during sterilization and continues to undergo gradual degradation and breakdown during storage, thus producing harmful aldehyde by-products such as, for example, formaldehyde, acetaldehyde, methylglyoxal etc. Thus, when these commercially prepared dialysate are introduced into the peritoneum of patients, these undesirable by-products and the acidity degrade the peritoneal membrane. It is relevant to note that an average peritoneal dialysis patient is infused with more than 3,000 liters of these non-biocompatible dialysis solutions per year.
Membrane damage reduces dialysis efficiency and most importantly, the length of time patients could be supported with peritoneal dialysis treatment. Patients who fail peritoneal dialysis treatment are transferred to hemodialysis. The annual cost of hemodialysis treatment may be twice as much as peritoneal dialysis. The end-stage renal disease cost containment is a major issue always at the table of the funding boards.
Clinical and animal research has identified the importance of replacing the current peritoneal dialysate with desirable alternatives that have normal pH, or higher pH near 7.2. Using current manufacturing methodologies, industries are having difficulties in re-producing desirable/beneficial dialysate that have been identified and clinically tested and proven effective over these recent years. And the selected few new dialysate that are available are priced beyond the budget of the clinics and the patients.
Thus, there is a need for a ready-to-use pre-fabricated bicarbonate dialysate, that is clinically more favorable than a glucose base solution and that is not subject to precipitation. Because of this problem desirable bicarbonate dialysate is commercially available in limited quantities and being sold at very high price.
Thus, it is an object of the present invention to overcome the deficiencies of the prior art.
Further and other objects of the invention will become apparent to those skilled in the art from reading the following summary of the invention and the preferred embodiments described and illustrated herein.